Conventionally, various attempts to evaluate the genetic activity or decode the biological process including a disease process or a biological process of pharmacological effect have been focused on genomics. However, proteomics can provide further information about the biological function of cells. Proteomics includes qualitative and quantitative measurement of the gene activity by detecting and quantifying the expression on a protein level rather than a gene level. Proteomics also includes a study of events which are not coded for gene, such as a post-translational modification of protein and an interaction between proteins.
At the present, it is possible to obtain an enormous volume of genome information. Accordingly, there is an increasing demand for high throughput proteomics. DNA chips have been come into practical use, as molecular arrays for this purpose. On the other hand, in order to detect proteins which are the most complicated and the most variable in biological functions, there are proposed protein chips, which are enthusiastically studied in these days. Protein chip is a collective term used to refer to any device in which protein or a molecule for catching such a protein is fixed on a surface of a chip (a fine substrate or particle).
However, the protein chips at present are generally developed as an extension of DNA chips. Therefore, attempts are made in order to fix a protein or a molecule for catching such a protein on a surface of a chip such as glass substrate or particle (e.g. Japanese Patent Application Laid-open No. 2001-116750).
It is considered that a nonspecific adsorption of a substance to be detected onto a substrate is one reason of decreasing the S/N ratio in detecting signals of protein chips (e.g. Hayashizaki, Y. and Okazaki, K., 2000, “Sure to Get data: Practical Manual of DNA Microarray”, pp. 57, Yodosha, Tokyo).
As a method of fixing proteins or the like, two methods are implemented at present. One is a fixing method based on a physical adsorption of protein. According to this method, adsorption preventing agents are coated in order to prevent a nonspecific adsorption of the secondary antibody after the protein is fixed. However, the ability of these agent for preventing the nonspecific adsorption is not sufficient. Furthermore, since the adsorption preventing agent is coated after the primary antibody is fixed, the coating is made on the fixed protein which prevents the reaction between the biochip and the secondary antibody. Thereby, there is a need for a biochip capable of restricting the nonspecific adsorption of biologically active substances without coating the adsorption preventing agent after the primary antibody is fixed.
In order to solve the problem above, there is a need for a biochip capable of restricting a nonspecific adsorption of biologically active substances. In the case that such a biochip is used, there is a problem that the protein or the molecule for catching the protein which is fixed on the substrate flows out in the washing process after the protein is caught, so that the signal is deteriorated. As one approach to the problem above, there is disclosed a method of coating an active component containing a functional group, a spacer group and a bonding group, a cross-liking component and a matrix-forming component on a support and curing them, so that a functional surface strongly bonded with the support can be formed on the support (e.g. Japanese Patent Application Kohyo (Laid-Open under national phase of PCT Application) No. 2004-531390). However, in this disclosed method, a curing of a low molecular component is proceeded on the support. Thereby, if the support is a plastic substrate, the support may be adversely warped or deformed. Furthermore, since a matrix is formed in the form of network, there are problems that the reaction of the functional group for fixing the biologically active substance may be adversely restricted, or that the reproducibility of the functional expression of the fixed biologically active substance is poor. Furthermore, the nonspecific adsorption is not always restricted sufficiently, because the protein infiltrated into the inside of the matrix is difficult to wash.